Lee, Pek Yen; (1993) Some studies on the effects of bradykinin and other bioactive peptides on mast cells. Doctoral thesis (Ph.D.), University College London (United Kingdom).

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Abstract

The effect of a number of serum-derived bioactive peptides on different histaminocytes was examined. Bradykinin induced a dose-dependent release of histamine and prostaglandin D2 from rat peritoneal mast cells. The release was rapid, non-cytotoxic, independent of extracellular calcium and inhibited by extremes of pH and temperature. A comparable release was produced by peptide analogues with both agonist and antagonist activity at conventional bradykinin receptors and by a range of other polybasic compounds. These data suggest that bradykinin may act through the putative mast cell polyamine receptor. Consistently, the release was inhibited by benzyldimethyltetradecylammonium chloride, was not accompanied by any change in intracellular cAMP levels and exhibited cross-tachyphylaxis with other polycations. Bradykinin also produced a synergistic enhancement of IgE-mediated histamine release from rat mast cells. The effects of bradykinin were highly species and site specific. Serosal mast cells of the rat and hamster were the most responsive, tissue mast cells of the rat and skin mast cells from man were weakly reactive, but other tissue mast cells and basophil leucocytes from man, together with mesenteric mast cells from the guinea pig, were refractory to the peptide. The anaphylatoxin C3a, des-arg-C3a and the analogue peptide 2IR also released histamine from rat peritoneal cells but had no effect on human lung or guinea pig mesenteric mast cells or, contrary to report in the literature, on human basophils. Thrombin produced a limited release of histamine from peritoneal cells of the rat but was without effect on these cells from the mouse, pulmonary and intestinal cells of the rat and human, basophils of man and bone marrow-derived mast cells of the mouse. In total, the present data show that a number of serum-derived peptides are able to induce histamine release from different mast cells. The effects are, however, very species and site specific and generally resemble those produced by other polyamines. On this basis, the possible role of these agents in allergic inflammation is discussed.

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